Biology direct · 2026
Single-cell analysis highlights the role of CD4+ IFN-I-related T cells in Behcet's uveitis during Interferonα-2a therapy.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Meiqi, Zhang Deyu, Huang Xue, Zhong Zhenyu, Wang Qingfeng, Liu Huan, Su Guannan, Jing Shixiang, Yang Tao, Li Na, Yang Peizeng
Аннотация
BACKGROUND: Behcet's disease (BD) involves multiple immune cells, but the mechanism by which interferon α-2a (IFNα-2a) exerts therapeutic effects on BD through immune cell modulation remains unclear. This study aimed to investigate the role of CD4 + IFN-I-related T cells in BD with active uveitis during IFNα-2a therapy.
METHODS: A single-cell atlas of peripheral blood mononuclear cells (PBMCs) was constructed from BD patients with active uveitis, post-4-month IFNα-2a therapy BD patients, active BD patients, and healthy controls (HCs) by integrating in-house and public scRNA-seq data. Bulk mRNA sequencing of CD4 + T cells from active BD patients and HCs was performed for validation. Cell-cell interaction, in vitro coculture, and inhibitor experiments were used to explore the underlying mechanisms.
RESULTS: CD4 + IFN-I-related T cells (characterized by high interferon-related gene expression) were significantly decreased in active BD patients but restored after IFNα-2a therapy. The LLT1-CD161 interaction intensity between CD4 + IFN-I-related T cells and NK cells was reduced in active BD and recovered post-therapy. CD4 + IFN-I-related T cells inhibited NK cell activation and IFN-γ secretion via the CD161 receptor.
CONCLUSIONS: IFNα-2a therapy reverses the decreased frequency of CD4 + IFN-I-related T cells in active BD, which in turn inhibits the inflammatory phenotype of NK cells through LLT1-CD161 interaction, providing new insights into the therapeutic mechanism of IFNα-2a in BD.
METHODS: A single-cell atlas of peripheral blood mononuclear cells (PBMCs) was constructed from BD patients with active uveitis, post-4-month IFNα-2a therapy BD patients, active BD patients, and healthy controls (HCs) by integrating in-house and public scRNA-seq data. Bulk mRNA sequencing of CD4 + T cells from active BD patients and HCs was performed for validation. Cell-cell interaction, in vitro coculture, and inhibitor experiments were used to explore the underlying mechanisms.
RESULTS: CD4 + IFN-I-related T cells (characterized by high interferon-related gene expression) were significantly decreased in active BD patients but restored after IFNα-2a therapy. The LLT1-CD161 interaction intensity between CD4 + IFN-I-related T cells and NK cells was reduced in active BD and recovered post-therapy. CD4 + IFN-I-related T cells inhibited NK cell activation and IFN-γ secretion via the CD161 receptor.
CONCLUSIONS: IFNα-2a therapy reverses the decreased frequency of CD4 + IFN-I-related T cells in active BD, which in turn inhibits the inflammatory phenotype of NK cells through LLT1-CD161 interaction, providing new insights into the therapeutic mechanism of IFNα-2a in BD.